Novel Compound Heterozygous RECQL4 Pathogenic Variants and Associated Phenotypes in a Chinese Patient With Rothmund-Thomson Syndrome: Case Report and Literature Review.
- 1Department of Medical Mycology, Center of Infectious Skin Diseases, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Abstract
Background
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, sparse hair, short stature, skeletal abnormalities, and an increased predisposition to malignancies. Pathogenic variants in the RECQL4 gene represent the most common genetic cause of RTS type 2. However, the full phenotypic spectrum, particularly regarding endocrine manifestations, remains incompletely understood.Objective
To report novel compound heterozygous RECQL4 pathogenic variant in a Chinese patient, describe a previously unreported endocrine phenotype (gynecomastia), and provide a comprehensive review of the literature regarding the RECQL4 mutational spectrum and differential diagnosis.Methods
A comprehensive clinical evaluation, including detailed physical examination, dermatoscopic assessment, and histopathological analysis, was performed. Whole-exome and Sanger sequencing were conducted to identify the causative variants. A literature review was additionally performed to contextualize the clinical and genetic findings.Results
A 14-year-old boy presented with classical poikiloderma, short stature, and an unreported feature of gynecomastia associated with low testosterone levels. Genetic testing identified compound heterozygous variants in RECQL4: a known nonsense variant c.2290C>T (p.Glu764*) and a novel frameshift variant c.2053del (p.Asp685Thrfs*5). Our literature review further delineated the differential diagnosis of poikiloderma among related genodermatoses and highlighted the systemic impact of RECQL4 dysfunction.Conclusion
The identification of the novel c.2053del variant broadens the known mutational landscape of RECQL4. Furthermore, the integration of our newly observed endocrine phenotype with a literature review underscores the necessity of multidisciplinary evaluation-including endocrinological, orthopedic, and audiological assessments-in the comprehensive management of RTS.
Related
- Hyperphosphatasia With Intellectual Disability (Mabry Syndrome) due to Compound Heterozygous PIGO Variants: First Molecularly Characterized Case in French Guiana: A Case Report and Review of the Literature.
- Compound‐Heterozygous PLVAP Missense Variants Associated With Attenuated Protein‐Losing Enteropathy (DIAR10)
- Novel compound heterozygous mutations of DOCK2 associated with early-onset recurrent infections
- Novel Compound Heterozygous CEP152 Variants Associated with Atypical Seckel Syndrome 5 in a Chinese Child: Functional Characterization of a Novel Splice-Site Variant and Expansion of the Genotype-Phenotype Spectrum.
- The Spectrum of Neurologic Phenotypes Associated With NUS1 Pathogenic Variants: A Comprehensive Case Series
BibTeX
@article{wang2026novel,
title = {{Novel Compound Heterozygous RECQL4 Pathogenic Variants and Associated Phenotypes in a Chinese Patient With Rothmund-Thomson Syndrome: Case Report and Literature Review.}},
author = {Yuanyuan Wang and Lulu Li and Chunjiao Zheng and Min Li and Qian Yu},
journal = {Molecular genetics \& genomic medicine},
year = {2026},
month = oct,
doi = {10.1002/mgg3.70320},
url = {https://europepmc.org/article/MED/42910491},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Novel Compound Heterozygous RECQL4 Pathogenic Variants and Associated Phenotypes in a Chinese Patient With Rothmund-Thomson Syndrome: Case Report and Literature Review.
AU - Yuanyuan Wang
AU - Lulu Li
AU - Chunjiao Zheng
AU - Min Li
AU - Qian Yu
PY - 2026
DA - 2026/10/01
JO - Molecular genetics & genomic medicine
DO - 10.1002/mgg3.70320
UR - https://europepmc.org/article/MED/42910491
AB - Background Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, sparse hair, short stature, skeletal abnormalities, and an increased predisposition to malignancies. Pathogenic variants in the RECQL4 gene represent the most common genetic cause of RTS type 2. However, the full phenotypic spectrum, particularly regarding endocrine manifestations, remains incompletely understood.Objective To report novel compound heterozygous RECQL4 pathogenic variant in a Chinese patient, describe a previously unreported endocrine phenotype (gynecomastia), and provide a comprehensive review of the literature regarding the RECQL4 mutational spectrum and differential diagnosis.Methods A comprehensive clinical evaluation, including detailed physical examination, dermatoscopic assessment, and histopathological analysis, was performed. Whole-exome and Sanger sequencing were conducted to identify the causative variants. A literature review was additionally performed to contextualize the clinical and genetic findings.Results A 14-year-old boy presented with classical poikiloderma, short stature, and an unreported feature of gynecomastia associated with low testosterone levels. Genetic testing identified compound heterozygous variants in RECQL4: a known nonsense variant c.2290C>T (p.Glu764*) and a novel frameshift variant c.2053del (p.Asp685Thrfs*5). Our literature review further delineated the differential diagnosis of poikiloderma among related genodermatoses and highlighted the systemic impact of RECQL4 dysfunction.Conclusion The identification of the novel c.2053del variant broadens the known mutational landscape of RECQL4. Furthermore, the integration of our newly observed endocrine phenotype with a literature review underscores the necessity of multidisciplinary evaluation-including endocrinological, orthopedic, and audiological assessments-in the comprehensive management of RTS.
SN - 2324-9269
ER -